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Disease modifying therapy impacts on miRNA expression profiling in peripheral blood from Relapsing-Remitting Multiple Sclerosis patients

ABSTRACT: Disease modifying therapy impacts on miRNA expression profiling in peripheral blood from Relapsing-Remitting Multiple Sclerosis patients

PROVIDER: PRJNA957301 | ENA |

REPOSITORIES: ENA

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Disease modifying therapy impacts on miRNA expression profiling in peripheral blood from Relapsing-Remitting Multiple Sclerosis patients

Project description:Multiple sclerosis (MS) is a chronic and progressive neurological disease. MS is characterized by early-stage neuroinflammation, neurodegeneration, and demyelination, with a spectrum of heterogeneous clinical manifestations in terms of disease course and response to therapy. The currently unsatisfied availability of diagnostic and prognostic biomarkers concerning disease progression and treatment response represents an important requirement for therapy individualization and drug efficacy. Specific Disease Therapies (DMTs) are available to prevent MS-related brain damage; however, the specific drug choice is still under debate and needs further characterization. Since differentially expressed miRNAs have been proposed as diagnostic tools in neurodegenerative/neuro-inflammatory diseases, such as multiple sclerosis, amyotrophic lateral sclerosis, and Alzheimer's disease, we characterized the miRNA expression profiling in peripheral blood mononuclear cells (PBMC) of subjects with relapsing-remitting MS treated with high efficacy DMTs: Cladribine (CLA, n=11 patients) or Ocrelizumab (OCRE, n=14 patients). The treated patients were compared to control (CTR) untreated subjects (n=15). Blood samples were collected from patients before treatment (time t0) and 6 months post-treatment (time t1), but just once from control subjects. CLA drug tablets were administered to the selected relapsing-remitting MS patients with a dosage of 1.75 mg/kg given for 5 days. OCRE drug was administered to the other relapsing-remitting MS patients by infusion with a dosage of 300 mg, twice in two weeks.

2024-01-03 | GSE230064 | GEO

Defective structural RNA processing in relapsing-remitting multiple sclerosis

Project description:It is fundamentally unknown how normal cellular processes or responses to extracellular stimuli may invoke polyadenylation and degradation of ncRNA substrates or if human disease processes exhibit defects in polyadenylation of ncRNA substrates as part of their pathogenesis. Our results demonstrate that mononuclear cells from subjects with relapsing-remitting multiple sclerosis (RRMS) exhibit pervasive increases in levels of polyadenylated ncRNAs including Y1 RNA, 18S and 28S rRNA, and U1, U2, and U4 snRNAs and these defects are unique to RRMS. Defects in expression of both Ro60 and La proteins in RRMS appear to contribute to increased polyadenylation of ncRNAs. Further, IFN-β1b, a common RRMS therapy, restores both Ro60 and La levels to normal as well as levels of polyadenylated Y1 RNA and U1 snRNA suggesting that aberrant polyadenylation of ncRNA substrates may have pathogenic consequences. We extracted RNA from peripheral whole blood in healthy control subjects and patients with established relapsing-remitting multiple sclerosis using PaxGene tubes.

2015-03-10 | E-GEOD-66573 | biostudies-arrayexpress

Defective structural RNA processing in relapsing-remitting multiple sclerosis

2015-03-10 | GSE66573 | GEO

Double-stranded Alu RNAs, type 1 IFN responses, and relapsing remitting multiple sclerosis

Project description:Double-stranded Alu RNAs, type 1 IFN responses, and relapsing remitting multiple sclerosis

| PRJNA521868 | ENA

Therapeutic efficacy of dimethyl fumarate in relapsing-remitting multiple sclerosis is linked with monocytic oxidative responses [Illumina]

Project description:Dimethyl fumarate (DMF) is a first-line-treatment for relapsing-remitting multiple sclerosis (RRMS). The redox master regulator Nrf2, essential in redox balance, is a target of DMF, but the precise therapeutic mechanisms remain elusive. Here we show impact of DMF on circulating monocytes and T cells in a prospective longitudinal RRMS patient cohort. DMF increased the level of oxidized isoprostanes in peripheral blood. Other observed changes, including methylome and transcriptome profiles, occur in monocytes prior to T cells. Importantly, monocyte counts and monocytic ROS increase following DMF and distinguish patients with beneficial treatment-response from non-responders. A single nucleotide polymorphism in the ROS-generating NOX3 gene is associated with beneficial DMF treatment-response and suggestively associated with increased ROS generation. Our data implicate monocyte-derived oxidative processes in autoimmune diseases and their treatment, and identify NOX3 genetic variant, monocyte counts and redox state as parameters potentially useful to inform clinical decisions on DMF therapy of RRMS.

2019-07-31 | GSE130491 | GEO

Therapeutic efficacy of dimethyl fumarate in relapsing-remitting multiple sclerosis is linked with monocytic oxidative responses [Affymetrix]

2019-07-31 | GSE130478 | GEO

Data in support of Temporal changes of inflammation and endothelial dysfunction in multiple sclerosis related to the evolution of enhancing lesions on frequent brain MRI

Project description:Blood-brain-barrier (BBB) breakdown and active inflammation by relapsing–remitting (RRMS) lesions are hallmarks of multiple sclerosis (MS). Leaky endothelial junctions causes an increased expression of circulating immune cells with associated adhesion molecules on endothelial cell membrane but also an increased production of endothelial derived extracellular microvesicles (EV). Methods: Relapsing–remitting MS (RRMS) patients with no disease-modifying treatment were monitored with weekly intervals using high-resolution 3T MRI scanning. Plasma samples from each measurement were analyzed for protein biomarkers of inflammation by quantitative proteomics, cytokines and chemokines using multiplex immunoassay. Extracellular microvesicles were characterized by an optimized endothelial stress EV Array analysis for detection of soluble secreted microvesicles.

2024-01-26 | PXD035422 | Pride

Therapeutic efficacy of dimethyl fumarate in relapsing-remitting multiple sclerosis is linked with monocytic oxidative responses

Project description:Therapeutic efficacy of dimethyl fumarate in relapsing-remitting multiple sclerosis is linked with monocytic oxidative responses

| PRJNA540471 | ENA

Therapeutic efficacy of dimethyl fumarate in relapsing-remitting multiple sclerosis is linked with monocytic oxidative responses [Illumina]

Project description:Therapeutic efficacy of dimethyl fumarate in relapsing-remitting multiple sclerosis is linked with monocytic oxidative responses [Illumina]

| PRJNA540475 | ENA

Therapeutic efficacy of dimethyl fumarate in relapsing-remitting multiple sclerosis is linked with monocytic oxidative responses [Affymetrix]

Project description:Therapeutic efficacy of dimethyl fumarate in relapsing-remitting multiple sclerosis is linked with monocytic oxidative responses [Affymetrix]

| PRJNA540434 | ENA

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